Up-regulation of 94-kDa glucose-regulated protein by hypoxia-inducible factor-1 in human endothelial cells in response to hypoxia

Sébastien Paris, Hélène Denis, Edouard Delaive, Marc Dieu, Valéry Dumont, Noëlle Ninane, Martine Raes, Carine Michiels

Research output: Contribution to journalArticle

Abstract

Hypoxic environment in solid tumor is known to favor cell survival and to initiate the formation of new capillaries. In this work, we identified by 2D gel analysis 94-kDa glucose-regulated protein (GRP94) as being upregulated in human endothelial cells in response to hypoxia. Three putative hypoxia responsive elements (HRE) were found in the GRP94 promoter. Competition experiments of HIF-1 DNA binding using specific probes containing each HRE sequence of the GRP94 promoter clearly evidenced that HIF-1 binds these sequences with high affinity. The human GRP94 promoter was then cloned upstream of the luciferase gene and showed enhanced activity in hypoxic conditions. Mutation of two of the three HREs present in this promoter completely inhibited the hypoxia-induced increase in luciferase activity. © 2004 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

Original languageEnglish
Pages (from-to)105-114
Number of pages10
JournalFEBS Letters
Volume579
Issue number1
DOIs
Publication statusPublished - 3 Jan 2005

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Keywords

  • Endothelial cell
  • GRP94
  • HIF-1
  • Hypoxia
  • Promoter

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